Interferons are single chain polypeptides secreted by most animal cells in response to a variety of inducers, including viruses, mitogens and polynucleotides. Interferons participate in regulation of cell function, and have antiviral, antiproliferative and immunomodulating properties. Native-human interferons are classified into three major types: .alpha.-IFN (leukocyte), IFN-.beta. (fibroblast) and .gamma.-IFN(immune). Native IFN-.beta. is produced primarily by diploid fibroblast cells and in lesser amounts by lymphoblastoid cells.
IFN-.beta. is a glycoprotein. Its nucleic acid and amino acid sequences have been determined. (Houghton et al., "The Complete Amino Acid Sequence of Human Fibroblast Interferon as Deduced Using Synthetic Oligodeoxyribonucleotide Primers of Reverse Transcriptase," Nucleic Acids Research, 8, pp. 2885-94 (1980); T. Taniguchi et al., "The Nucleotide Sequence of Human Fibroblast DNA," Gene, 10, pp. 11-15 (1980)). Recombinant IFN-.beta. has been produced and characterized.
IFN-.beta. exhibits various biological and immunological activities. One of IFN-.beta.'s biological activities is its antiviral activity. This antiviral activity can be neutralized by antibodies to IFN-.beta.. See EP-B1-41313. Preparation and purification of antibodies to IFN-.beta. is described in EP-B1-41313 and the references cited therein. IFN-.beta. is also able to bind to cells that express interferon receptors, such as Daudi cells or A549 cells.
As a result of these activities, IFN-.beta. has potential applications in immunotherapy, antitumor and anticancer therapies, and antiviral therapies.
Numerous investigations and clinical trials have been and continue to be conducted into the antitumor and anticancer properties of both wild type and recombinant IFN-.beta.. These include treatment of several malignant diseases such as osteosarcoma, basal cell carcinoma, cervical dysplasia, glioma, acute myeloid leukemia, multiple myeloma and Hodgkin's disease. In addition, IFN-.beta. has been shown to cause local tumor regression when injected into subcutaneous tumoral nodules in melanoma and breast carcinoma-affected patients.
IFN-.beta. (wild-type and recombinant) has been tested clinically in a variety of viral infections, including papilloma viruses, such as genital warts and condylomata of the uterine cervix; viral hepatitis, including acute/chronic hepatitis B and non-A, non-B hepatitis (hepatitis C); herpes genitalis; herpes zoster; herpetic keratitis; herpes simplex; viral encephalitis; cytomegalovirus pneumonia; and in the prophylaxis of rhinovirus.
Clinical trials using recombinant IFN-.beta. in the treatment of multiple sclerosis have also been conducted and IFN-.beta. is approved for sale in the United States for the treatment of multiple sclerosis.